This #CTD2019, there is much to celebrate.
A guest blog by Dr. Sheryl A. Kingsberg, PhD, IF
Chief, Division of Behavioral Medicine, Department of OB/GYN, MacDonald Women’s Hospital
Professor, Departments of Reproductive Biology and Psychiatry, Case Western Reserve University School of Medicine
Clinical Trials Day, on May 20, is an opportunity for our industry to celebrate the accomplishments we’ve achieved through clinical research, and to consider the work remaining to be done. This year I think it is especially important to acknowledge the progress we’ve made in support of women’s sexual health.
For years, many medical issues related to female sexual dysfunction and women’s reproductive health have been largely ignored by the research community. But in the past few years, we’ve seen a trend start to shift.
• In 2015, after twice rejecting it, the US Food and Drug Administration (FDA) approved flibanserin (Addyi) for the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women. It is the first drug ever approved to treat HSDD in premenopausal women.
• In 2018, FDA accepted AMAG Pharmaceuticals’ new drug application for bremelanotide, another treatment for HSDD in premenopausal women. The NDA submission was backed by clinical data from two large phase 3 studies demonstrating statistically significant improvement in desire and decreased distress associated with low desire compared to placebo.
• In 2018, Daré Bioscience, in partnership with Strategic Science & Technologies, announced plans for a content validity study of Sildenafil Cream, a topical treatment for women with Female Sexual Arousal Disorder (FSAD). This content validity study will explore the use of specific patient reported outcome (PRO) measures for the Phase 2b and Phase 3 studies. Sildenafil is the active ingredient in Viagra.
These are exciting advances, particularly as these conditions affect a huge swath of the female adult population. Prevalence surveys estimate that about one in ten women have HSDD.
However, sponsors still face many barriers in developing treatments for female sexual dysfunction which delay progress on these important research endeavors. Lack of agreement on relevant endpoints, lack of conversations between clinicians and patients about healthy sexual function, difficulty recruiting women to these trials, and long standing biases against bringing women into clinical research have all created unnecessary obstacles and poor research choices.
Federal regulators often require stratifying subjects by menopausal status even in trials for non-hormonal treatments barring a significant portion of older women from participating despite the fact that they are part of the target patient population. Trials for drugs treating male sexual dysfunction have no such age distinction burdens.
There has also been considerable debate about relevant endpoints for these studies and how to measure them. Some experts argue that study participants should keep daily diaries about their level of desire. However these data collection activities have not been validated as appropriate ways to measure desire, and can result in diary fatigue and diary non-compliance which may cloud results – this was one of the reasons flibanserin was originally rejected by the FDA. There is also disagreement about the relevance of counting sexual encounters (SSEs) as an endpoint measure, as there are many reasons women may have sex with their partners without feeling desire.
However, we are seeing progress around all of these issues. The FDA has actively sought feedback from sexual health professionals to better understand how to design effective trials for these conditions. These dialogs led FDA leaders to agree that counting sexual encounters is not required to be a primary endpoint and are focusing patient reported outcome measures on desire and the level of distress associated with sexual dysfunction as the most relevant endpoints to measure. They’ve also designated HSDD and/or female sexual arousal/interest disorder (FSAID) as an unmet medical need, and developed draft guidance on how to design phase III trials for drugs to treat this condition.
Perhaps more importantly, we are seeing many pharmaceutical companies investing more time and resources into identifying treatments for woman’s sexual health conditions, in recognition of the potential benefits that can be derived from addressing unmet medical needs that affect millions of women.
This makes me optimistic about the future of clinical research, and hopeful that conversations about female sexual dysfunction and treatment options will finally become a normal part of the healthcare conversation.